title: Myocardin-related transcription factor A is up-regulated by 17β-estradiol and promotes migration of MCF-7 breast cancer cells via transactivation of MYL9 and CYR61.
abstract: Many lines of evidence have suggested that estrogen plays important roles not only in the initiation and proliferation of breast cancer, but also in cancer metastasis. However, the mechanistic basis of the latter events is poorly understood. In addition, recent studies have suggested that myocardin-related transcription factor A (MRTF-A) might be related to cancer metastasis. However, as reports are contradictory, certain of its roles still remain confusing. In the present study, we showed that excessive 17β-estradiol could promote the migration of MCF-7 breast cancer cells and up-regulate the expression of MRTF-A, myosin regulatory light chain 9 (MYL9), and cysteine-rich angiogenic inducer 61 (CYR61). Overexpression of MRTF-A significantly promoted the migration of MCF-7 cells through its transactivation effects on MYL9 and CYR61 genes, while RNA interference-mediated knockdown of MRTF-A strongly inhibited transcription and expression of the target genes and reduced the migration ability of MCF-7 cells. These results provided novel evidence supporting the metastasis-promoting functions of MRTF-A, and implied that MRTF-A might be a switch for the estrogen pathway to change its proliferation-promoting roles into migration-stimulating roles in breast cancer.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Xuegang
authors.initials: X
authors.lastname: Luo
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Guo
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhao
authors.forename: Ai
authors.initials: A
authors.lastname: Mu
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Tongcun
authors.initials: T
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D055515:Cysteine-Rich Protein 61 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004958:Estradiol / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D018994:Myosin Light Chains / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D004268:DNA-Binding Proteins; C431575:MRTFA protein, human; D018994:Myosin Light Chains; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D004958:Estradiol
keywords: 17β-estradiol; CYR61; MRTF-A; MYL9; breast cancer; migration